High-affinity Cu(I) ligands and methods of use thereof
Inventors
Fahrni, Christoph J. • MORGAN, M. Thomas
Assignees
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Publication Number
US-12630573-B2
Publication Date
2026-05-19
Expiration Date
Abstract
Several dimethylphosphine sulfide- and phosphine-containing compounds have been discovered that chelate copper(I) with high affinity. In certain embodiments, the compounds can be used to quantify copper(I) in complex biological systems. In another embodiment, the compounds can be used for the treatment of copper(I)-related illnesses and conditions. In still other embodiments, the compounds are ratiometric probes.
Core Innovation
The disclosure provides copper-chelating dimethylphosphine sulfide and phosphine ligands, including phenPS, naphPS, ratiometric probe designs, a Formula VI benzoic-acid derivative, and related conjugates. In particular, a compound of formula (V) comprises a 5- or 6-membered aryl or heteroaryl ring A, R1 as —H, R2 as —COOH, —COO(C1-C30 alkyl), or —CONH(C1-C30 alkyl), and R3 as —C1-C30 alkyl, including enantiomers, polymorphs, or salts thereof. PhenPS binds Cu(I) in a 1:1 complex exhibiting a reported log K of 21.21 and Kd of 0.6 zM.
The disclosure details analyte-responsive phenPS compounds, such as phenPS-acetamide, showing absorption changes with analyte concentration, and describes Crisp-17 as a fluorescent cellular Cu(I) sensor. Agarose-immobilized phenPS selectively removes copper from supplemented culture medium and cell lysate. The text further proposes copper removal for cancer treatment using tumor-targeted conjugates without reporting cancer-treatment results, and the background problem solved is not explicitly described in the patent.
Claims Coverage
The claims identify one independent claim directed to one inventive feature comprising a defined compound of formula (V).
Compound of formula (V)
A compound in which A is any 5- or 6-membered aryl or heteroaryl ring, R1 is —H, R2 is —COOH, —COO(C1-C30 alkyl), or —CONH(C1-C30 alkyl), and R3 is a —C1-C30 alkyl, including an enantiomer, polymorph, or salt thereof.
The independent claim covers the formula (V) compound across the specified ring, substituent, and form alternatives, including its enantiomers, polymorphs, and salts.
Stated Advantages
PhenPS is reported to bind Cu(I) with a log K of 21.21 ± 0.09, and agarose-immobilized phenPS selectively removes copper from supplemented culture medium and cell lysate.
Documented Applications
Crisp-17 is demonstrated as a fluorescent cellular Cu(I) sensor.
PhenPS-agarose is described for selectively removing copper from supplemented culture medium and cell lysate.
Copper removal is proposed as a cancer-treatment approach using tumor-targeted conjugates, without reported cancer-treatment results.
Pharmaceutical compositions comprising one or more claimed compounds, and small biomolecules used to conjugate detection labels, proteins, or aptamers.
Cellular and metal-detection assays, as illustrated by cell-associated measurements and metal-associated signals.
Copper detection, quantification, and imaging in samples and cells.
Copper removal or delivery in copper-related disorders.
Industrial or environmental copper chelation.
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